Analyzing the Loss and the Recovery of Consciousness: Functional Connectivity Patterns and Changes in Heart Rate Variability During Propofol-Induced Anesthesia.

The analysis of the central and the autonomic nervous systems (CNS, ANS) activities during general anesthesia (GA) provides fundamental information for the study of neural processes that support alterations of the consciousness level. In the present pilot study, we analyzed EEG signals and the heart rate (HR) variability (HRV) in a sample of 11 patients undergoing spinal surgery to investigate their CNS and ANS activities during GA obtained with propofol administration. Data were analyzed during different stages of GA: baseline, the first period of anesthetic induction, the period before the loss of consciousness, the first period after propofol discontinuation, and the period before the recovery of consciousness (ROC). In EEG spectral analysis, we found a decrease in posterior alpha and beta power in all cortical areas observed, except the occipital ones, and an increase in delta power, mainly during the induction phase. In EEG connectivity analysis, we found a significant increase of local efficiency index in alpha and delta bands between baseline and loss of consciousness as well as between baseline and ROC in delta band only and a significant reduction of the characteristic path length in alpha band between the baseline and ROC. Moreover, connectivity results showed that in the alpha band there was mainly a progressive increase in the number and in the strength of incoming connections in the frontal region, while in the beta band the parietal region showed mainly a significant increase in the number and in the strength of outcoming connections values. The HRV analysis showed that the induction of anesthesia with propofol was associated with a progressive decrease in complexity and a consequent increase in the regularity indexes and that the anesthetic procedure determined bradycardia which was accompanied by an increase in cardiac sympathetic modulation and a decrease in cardiac parasympathetic modulation during the induction. Overall, the results of this pilot study showed as propofol-induced anesthesia caused modifications on EEG signal, leading to a "rebalance" between long and short-range cortical connections, and had a direct effect on the cardiac system. Our data suggest interesting perspectives for the interactions between the central and autonomic nervous systems for the modulation of the consciousness level.

Piezoelectric Surgery for Dorsal Spine.

BACKGROUND: Laminoplasty and laminectomy are 2 common surgical procedures used in treating degenerative and neoplastic diseases of the spinal canal. Routinely used instruments, such as the Kerrison rongeur and high-speed drill, can result in potentially serious complications, such as dural injury and thermal and mechanical damage to neurovascular structures. We adopted piezoelectric bone surgery, which permits a selective cut of mineralized tissues, to perform posterior procedures on the thoracic spine, where the relationship between bone and the spinal cord is critical. The aim of this article was to evaluate the use of piezoelectric surgery for performing dorsal spine laminectomy and laminoplasty. METHODS: The Mectron piezosurgery device was developed for cutting bone with microvibrations that are created by the piezoelectric effect. This instrument allows a safe and precise bone cut, and it is characterized by no heat generation, thus avoiding thermal injury to bone and soft tissues. We used this device to perform 8 laminoplasties for tumors of the dorsal spine and 2 laminectomies for thoracic spinal stenosis in 10 patients. RESULTS: There were no procedure-related intraoperative complications, such as dural injury or damage to neural structures. CONCLUSIONS: The piezoelectric device showed excellent results in terms of safety and precise bone cutting properties when performing posterior surgical procedures in the dorsal spine, where thermal injury produced by the conventionally used drill may damage the spinal cord closer to bony elements.

Patients' reported outcome measures and clinical scales in brain tumor surgery: results from a prospective cohort study.

BACKGROUND: This study aims to assess surgical outcome in brain tumor surgery using patient reported outcome measures (PROMs) and to compare their results with traditional clinical outcome measurements. METHOD: Neuro-oncological patients undergoing surgical removal for the lesion were enrolled; MOCA test, PROMs (EUROHIS-QoL, PGWB-S, WHODAS-12), and the clinical scale Karnofsky Performance Status (KPS) were administered to evaluate respectively cognitive status, quality of life, well-being, disability, and functional status before surgery and at 3-month follow-up. Wilcoxon test was performed to evaluate the longitudinal change of test scores, the smallest detectable difference to classify the change of patients in PROMs, the Cohen kappa to investigate the concordance between KPS and PROMs in classifying the patients' change, and Mann-Whitney U test to compare patients with complications and no complications. RESULTS: A total of 101 patients were enrolled (54 woman, mean age 50.2 ± 14.1, range 20-85): psychological well-being improved at follow-up; 95 patients (94.1%) were improved/unchanged and 6 (5.9%) were worsened according to PROMs; functional status measured with KPS had a slight agreement with quality of life and disability and no agreement with psychological well-being questionnaires; patients with complications had a greater worsening in KPS. CONCLUSIONS: According to PROMs measuring QoL, disability, and psychological well-being, most of the patients were improved/unchanged after surgery. Since PROMs and KPS detect different aspects of the patients' health status, PROMs should be integrated in surgical outcome evaluation. Furthermore, their association with complications and with other clinical and subjective variables that could influence patient's perception of health status should be investigated.

Fluorescein-Guided Surgery for Resection of High-Grade Gliomas: A Multicentric Prospective Phase II Study (FLUOGLIO).

Purpose: Sodium fluorescein is a dye that, intravenously injected, selectively accumulates in high-grade glioma (HGG) tissue through a damaged blood-brain barrier. In this article, the final results of a multicentric prospective phase II trial (FLUOGLIO) on fluorescein-guided HGG resection through a dedicated filter on the surgical microscope were reported.Methods: Patients with suspected HGGs considered suitable for removal were eligible to participate in this trial. Fluorescein was intravenously injected at a dose of 5 to 10 mg/kg. The primary endpoint was the percentage of patients with histologically confirmed HGGs, without contrast-enhancing tumor at the immediate postoperative MRI. Secondary endpoints were PFS, residual tumor on postoperative MRI, overall survival, neurologic deficits, and fluorescein-related toxicity. The sensitivity and specificity of fluorescein in identifying tumor tissue were estimated by fluorescent and nonfluorescent biopsies at the tumor margin. The study was registered on the European Regulatory Authorities website (EudraCT 2011-002527-18).Results: Fifty-seven patients aged 45 to 75 years were screened for participation, and 46 were considered for primary and secondary endpoints. Mean preoperative tumor volume was 28.75 cm3 (range, 1.3-87.8 cm3). Thirty-eight patients (82.6%) underwent a complete tumor removal. Median follow-up was 11 months. PFS-6 and PFS-12 were 56.6% and 15.2%. Median survival was 12 months. No adverse reaction related to SF administration was recorded. The sensitivity and specificity of fluorescein in identifying tumor tissue were respectively 80.8% and 79.1%.Conclusions: Fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and enables a high percentage of contrast-enhancing tumor in patients with HGGs. Clin Cancer Res; 24(1); 52-61. ©2017 AACR.

Predicting functional impairment in brain tumor surgery: the Big Five and the Milan Complexity Scale.

OBJECT The Milan Complexity Scale-a new practical grading scale designed to estimate the risk of neurological clinical worsening after performing surgery for tumor removal-is presented. METHODS A retrospective study was conducted on all elective consecutive surgical procedures for tumor resection between January 2012 and December 2014 at the Second Division of Neurosurgery at Fondazione IRCCS Istituto Neurologico Carlo Besta of Milan. A prospective database dedicated to reporting complications and all clinical and radiological data was retrospectively reviewed. The Karnofsky Performance Scale (KPS) was used to classify each patient's health status. Complications were divided into major and minor and recorded based on etiology and required treatment. A logistic regression model was used to identify possible predictors of clinical worsening after surgery in terms of changes between the preoperative and discharge KPS scores. Statistically significant predictors were rated based on their odds ratios in order to build an ad hoc complexity scale. For each patient, a corresponding total score was calculated, and ANOVA was performed to compare the mean total scores between the improved/unchanged and worsened patients. Relative risk (RR) and chi-square statistics were employed to provide the risk of worsening after surgery for each total score. RESULTS The case series was composed of 746 patients (53.2% female; mean age 51.3 ± 17.1). The most common tumors were meningiomas (28.6%) and glioblastomas (24.1%). The mortality rate was 0.94%, the major complication rate was 9.1%, and the minor complication rate was 32.6%. Of 746 patients, 523 (70.1%) patients improved or remained unchanged, and 223 (29.9%) patients worsened. The following factors were found to be statistically significant predictors of the change in KPS scores: tumor size larger than 4 cm, cranial nerve manipulation, major brain vessel manipulation, posterior fossa location, and eloquent area involvement (Nagelkerke R(2) = 0.286). A grading scale was obtained with scores ranging between 0 and 8. Worsened patients showed mean total scores that were significantly higher than the improved/unchanged scores (3.24 ± 1.55 vs 1.47 ± 1.58; p < 0.001). Finally, a grid was developed to show the risk of worsening after surgery for each total score: scores higher than 3 are suggestive of worse clinical outcome. CONCLUSIONS Through the evaluation of the 5 aforementioned parameters-the Big Five-the Milan Complexity Scale enables neurosurgeons to estimate the risk of a negative clinical course after brain tumor surgery and share these data with the patient. Furthermore, the Milan Complexity Scale could be used for research and educational purposes and better health system management.

Change in quality of life, disability, and well-being after decompressive surgery: results from a longitudinal study.

The aim of this study is to evaluate quality of life (QoL), disability, and psychological well-being (PWB) in patients with disc herniation and stenosis before and after decompressive surgery and to investigate factors associated with an improvement in the postoperative disability level. An observational longitudinal study was carried out to collect preoperative and postoperative data on QoL, disability, and PWB using European Health Interview Survey-Quality of Life (EUROHIS-QoL), WHO Disability Assessment Schedule, second version (WHODAS-II), and Psychological General Well-Being Index-Short (PGWB-S) questionnaires. Friedman's analysis of variance was performed to compare preoperative and postoperative test scores, whereas a one-sample t-test was calculated to compare the mean test scores with the general population. A hierarchical logistic regression was developed to investigate the association between the change in the disability level after surgery, sociodemographic and clinical characteristics, and preoperative test scores. Complete data were available for 55 patients. PGWB-S and WHODAS-II scores improved significantly (P=0.004 and 0.003), even if the disability level remained high after surgery. The logistic regression showed that patients with worse preoperative WHODAS-II scores had higher odds achieving improvement in their disability level after surgery. This study showed that disability and PWB improve significantly after surgery, but further treatment and a healthy lifestyle are expected and recommended as the disability level remains high. In addition, more severe preoperative disability was a predictor of better clinical outcome.

The Impact of Neurosurgical Complications on Patients' Health Status: A Comparison Between Different Grades of Complications.

OBJECTIVE: The aim of this article is to investigate the frequency of neurosurgical complications according to Landriel-Ibañez Classification and their impact on patients' health status. METHODS: Patients undergoing neurosurgical procedures were enrolled in an observational longitudinal study at Neurological Institute Carlo Besta from January 2012 to September 2013. We evaluated patients' health status before surgery, at discharge, and follow-up with the Karnofsky Performance Status Scale (KPS), whereas the Landriel-Ibañez Classification was used to record complications. Descriptive statistics were performed to illustrate the distribution of sociodemographic and clinical data. We used nonparametric tests to compare KPS scores of patients with different grades of complication and to evaluate the differences between preoperative KPS scores, KPS scores at discharge and follow-up. The effect sizes were also calculated. RESULTS: We enrolled 1008 patients. We registered 228 complications (139 grade 1 complications, 63 grade 2 complications, 20 grade 3 complications, and 6 grade 4 complications). All patients with a complication showed KPS scores at discharge that were lower than preoperative scores and KPS scores at follow-up greater than scores at discharge. After patients with grade 4 complications, who had the worst outcomes, those with grade 3 complications were the most compromised after surgery whereas patients with grade 2 complications seemed to have a better health status than patients with grade 1 complication. CONCLUSIONS: Our study highlights the impact of neurosurgical complications on patients' life and contributes to the debate on how define and classify adverse events because a classification only based on treatment seems to be not adequate.

Quality of life measures in Italian neurosurgical patients: validity of the EUROHIS-QOL 8-item index.

PURPOSE: To assess the validity, reliability and factor structure of the Italian version of the EUROHIS-QOL (European Health Interview Survey-Quality of Life) 8-item index in patients who are potential candidates for neurosurgical procedures. METHODS: Cross-sectional study. Patients completed the EUROHIS-QOL 8-item index, a disability and general well-being questionnaire; the Karnofsky performance status scale (KPS) was used as a general measure of functional status. Factor analysis was used to confirm the one-factor structure of the EUROHIS-QOL 8-item index. Reliability was measured using Cronbach's alpha coefficient, item-total correlation and inter-item correlation. Construct validity was assessed with Pearson's coefficient (expected to be below 0.70) and known-group analysis, dividing patients between those KPS >90 and KPS ≤90 (the latter expected to report lower QoL). RESULTS: The one-factor structure was partly confirmed, with two items having low loadings. Cronbach's alpha was 0.78; item-total correlations were below 0.70; and average inter-item correlation was 0.309. Correlations were all significant and moderate; known-group analysis shows that QoL scores were lower in patients with active symptoms (KPS ≤90). CONCLUSIONS: Our findings partly confirm the factor structure and reliability of the EUROHIS-QOL 8-item index, which suggests that it may be a useful and straightforward quality of life measurement technique in neurosurgical departments.

Quality of life, disability, well-being, and coping strategies in patients undergoing neurosurgical procedures: preoperative results in an Italian sample.

BACKGROUND: The aim of this paper is to present the preliminary results of QoL, well-being, disability, and coping strategies of patients before neurosurgical procedure. METHODS: We analysed data on preoperative quality of life (EUROHIS-QoL), disability (WHODAS-II), well-being (PGWB-S), coping strategies (Brief COPE), and functional status (KPS score) of a sample of patients with brain tumours and cerebrovascular and spinal degenerative disease admitted to Neurological Institute Carlo Besta. Statistical analysis was performed to illustrate the distribution of sociodemographic and clinical data, to compare mean test scores to the respective normative samples, and to investigate the differences between diagnoses, the correlation between tests, and the predictive power of sociodemographic and clinical variables of QoL. RESULTS: 198 patients were included in the study. PGWB-S and EUROHIS-QoL scores were significantly lower than normative population. Patients with spinal diseases reported higher scores in WHODAS-II compared with oncological and cerebrovascular groups. Finally sociodemographic and clinical variables were significant predictors of EUROHIS-QoL, in particular PGWB-S and WHODAS-II. CONCLUSION: Our preliminary results show that preoperatory period is critical and the evaluation of coping strategies, quality of life, disability, and well-being is useful to plan tailored intervention and for a better management of each patient.

Disability in Italian neurosurgical patients: validity of the 12-item World Health Organization Disability Assessment Schedule.

The aim of the study was to assess factor structure, internal consistency and validity of the Italian version of the World Health Organization Disability Assessment Schedule 12-item version (WHODAS-12) in patients scheduled for neurosurgical procedures for brain tumours, cerebrovascular or spinal diseases. Disability was assessed with the WHODAS-12, quality of life with the eight-item European Health Interview Survey-Quality of Life, well-being with the Psychological General Well-Being Index-Short and general health with the Karnofsky Performance Status (KPS) scales. Factor analysis was used to confirm WHODAS-12 one-factor structure; root mean square error of approximation (RMSEA) and χ2/d.f. ratio were used to test the model fit. Internal consistency was assessed with Cronbach's α coefficient, item-total correlation and interitem correlation; convergent validity was assessed with Pearson's coefficient and discriminative validity was assessed with the t-test, dividing patients between those with KPS greater than 90 and KPS of 90 or less. The one-factor structure was confirmed (RMSEA=0.079; χ2/d.f.=2.16) and internal consistency was adequate. Correlations between the three outcome measures were significant, negative and moderate; the t-test showed disability scores to be statistically significantly higher in patients with KPS of 90 or less. Our results confirm factor structure and validity of WHODAS-12 in Italian neurosurgical inpatients; we therefore support its use in neurosurgery departments.

Is fluorescein-guided technique able to help in resection of high-grade gliomas?

OBJECT: Fluorescein, a dye that is widely used as a fluorescent tracer, accumulates in cerebral areas where the blood-brain barrier is damaged. This quality makes it an ideal dye for the intraoperative visualization of high-grade gliomas (HGGs). The authors report their experience with a new fluorescein-guided technique for the resection of HGGs using a dedicated filter on the surgical microscope. METHODS: The authors initiated a prospective Phase II trial (FLUOGLIO) in September 2011 with the objective of evaluating the safety of fluorescein-guided surgery for HGGs and obtaining preliminary evidence regarding its efficacy for this purpose. To be eligible for participation in the study, a patient had to have suspected HGG amenable to complete resection of the contrast-enhancing area. The present report is based on the analysis of the short- and long-term results in 20 consecutive patients with HGGs (age range 45-74 years), enrolled in the study since September 2011. In all cases fluorescein (5-10 mg/kg) was injected intravenously after intubation. Tumor resection was performed with microsurgical technique and fluorescence visualization by means of BLUE 400 or YELLOW 560 filters on a Pentero microscope. RESULTS: The median preoperative tumor volume was 30.3 cm(3) (range 2.4-87.8 cm(3)). There were no adverse reactions related to fluorescein administration. Complete removal of contrast-enhanced tumor was achieved in 80% of the patients. The median duration of follow-up was 10 months. The 6-months progression-free survival rate was 71.4% and the median survival was 11 months. CONCLUSIONS: Analysis of these 20 cases suggested that fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and allows a high rate of complete resection of contrast-enhanced tumor as determined on early postoperative MRI. Clinical trial registration no.: 2011-002527-18 (EudraCT).

Fluorescein-guided surgery for grade IV gliomas with a dedicated filter on the surgical microscope: preliminary results in 12 cases.

BACKGROUND: Fluorescein is widely used as a fluorescent tracer for many applications. Its capability to accumulate in cerebral areas with blood-brain barrier damage makes it an ideal dye for intraoperative visualization of malignant gliomas (MG). We report our preliminary experience in fluorescein-guided removal of grade IV gliomas using a dedicated filter on the surgical microscope. METHODS: In September 2011 we started a prospective phase II trial (FLUOGLIO) to evaluate the safety and obtain initial indications about the efficacy of fluorescein-guided surgery for MG. Patients with suspected MG amenable to complete resection of contrast-enhancing areas were eligible to participate in this study. This report is based on a preliminary analysis of the results of 12 patients with grade IV gliomas out of 15 consecutive cases (age range 48-72 years) enrolled since September 2011. Fluorescein was injected intravenously (i.v.) after intubation (5-10 mg/kg). The tumor was removed using a microsurgical technique and fluorescence visualization by BLU 400 or YELLOW 560 filters on a Pentero microscope (Carl Zeiss, Germany). The study was approved by our ethics committee and registered on the European Regulatory Authorities website (EudraCT no. 2011-002527-18). RESULTS: Histological analysis confirmed grade IV gliomas in 12/15 cases. Median preoperative tumor volume was 33.15 cm(3) (9.6-87.8 cm(3)). No adverse reaction related to the administration of fluorescein was registered. Contrast-enhanced tumor was completely removed in 75 % of the patients. CONCLUSION: This preliminary analysis suggested that the use of intravenous fluorescein during surgery on grade IV gliomas is safe and allows a high rate of complete resection of contrast-enhanced tumor at the early postoperative MRI.

Expression of neural and neurotrophic markers in nucleus pulposus cells isolated from degenerated intervertebral disc.

Intervertebral disc (IVD) degeneration is a common disorder of the lower spine. Since it is caused by loss of cellularity, there is interest in the comprehension of the cellular phenotypes. This study aimed to verify if stem cells isolated from nucleus pulposus of intervertebral discs (NPs-IVD), which may express neurogenic properties, may be implicated in IVD disease. NPs-IVD isolated from 14 human pathological discs were cultured under mesenchymal and neural differentiation. An induction of the neural markers GFAP, NF, MAP2, O4, and a decrement of the expression of the immature neural markers ß-tubulin III, Nestin, NG2, occurred within the neural differentiation. The expression of TrkA and p75NGFR, the receptors of NGF, was not correlated with neural induction; in contrast, TrkB, the BDNF receptor, increased and was co-expressed with acid sensing ion channel 3 (ASIC3). In the same condition, neuroinflammatory markers were over-expressed. We confirm our hypothesis that stem cells within IVD degeneration acquire neurogenic phenotype, causing the induction of markers related to inflammatory condition. These cells could promote the enrolment of neurotrophines in adaptation to the acidic microenvironment in degenerative conditions. These data could improve our knowledge about IVD cellularity and eventually lead to the development of pharmacological therapies.

Tethered cord: natural history, surgical outcome and risk for Chiari malformation 1 (CM1): a review of 110 detethering.

The surgical results of this series of occult spina bifida seem better than the natural history registered in the long pre-operative period in terms of neurological deterioration. The major contribution to this result is attributed to neurophysiological monitoring that lowers the risks of permanent damage and increases the percentage of effective detethering. The present series of TCS, due to conus and filar lipoma, documents that CM1 is a really rare association occurring in less than 6% of the patients, despite the low position of conus. The detethering procedure did not influence the tonsillar position, thus excluding the correlation between the tethering and the tonsillar descent. The genetic alteration documented in a girl reinforces the hypothesis of a rare complex polymaformative picture deserving multiple procedures according to the prevailing clinical symptoms.

Treatment for Chiari 1 malformation (CIM): analysis of a pediatric surgical series.

Children may present a peculiar picture of CIM, as syncopes and acute paraparesis. In a series of 99 children operated for CIM at FINCB there were no major surgical morbidity nor mortality. The preoperative symptoms improved more in this pediatric series than in the adult cases treated at the same institution in the same period; a reason could be the shorter duration of symptoms and another the children plasticity. An untreated nonsyndromic craniosynostosis was present in 10 cases. In our hands, the results of the limited extradural decompression were poor. In some CIM associated with psychiatric symptoms an unexpected improvement was observed after tonsilar resection. The associated Syringomyelia reduced in more than 80% of children and disappeared in a significant number. The rare associated tethered cord (5%) needed a double treatment, detethering by itself being insufficient to treat also tonsillar descent. The clinical symptoms are often more serious in children than in the adults, but the results of surgery, especially on the syrinx, are better.

The role of intraoperative electromyographic monitoring in lumbosacral lipomas.

OBJECTIVE: To demonstrate the role of intraoperative multichannel electromyographic (EMG) monitoring to reduce postoperative deterioration and achieve full untethering of complex occult dysraphisms. METHODS: A retrospective analysis was performed on 66 patients who underwent operation for lumbosacral lipomas. Twenty recent cases were submitted to EMG monitoring and stimulation. RESULTS: All patients presented symptoms at the time of surgery, and 74% exhibited progressive deterioration during the lengthy preoperative period. Postoperative surgery-related deterioration was observed in 6% of patients. This number was reduced to zero with the introduction of intraoperative EMG monitoring. CONCLUSION: Intraoperative multichannel EMG monitoring can be carried out and requires only minimal changes to anesthetic procedures. With this method, it is possible to better identify the neural structures of complex malformations, reducing the risks of surgical damage and incomplete detethering.